Updated Preclinical Data Support Potential of First AAV-Based Gene Therapy as a Treatment for Adrenomyeloneuropathy

PHILADELPHIA--(BUSINESS WIRE)-- SwanBio Therapeutics, a gene therapy company advancing AAV-based therapies for the treatment of devastating, inherited neurological conditions, today presented updated data from studies of the company’s lead candidate in non-human primates (NHPs) and rodent models. These data support the potential of SBT101 as a treatment for adrenomyeloneuropathy (AMN), a progressive, inherited, and debilitating neurodegenerative disease caused by a deficiency in the ABCD1 gene which primarily affects the spinal cord.

The findings presented at the American Academy of Neurology (AAN) 2022 Annual Meeting in Seattle build on previously reported data, showing on-target effects across multiple measurements in both NHPs and mouse models, and dose-dependent biodistribution of SBT101 with a favorable safety profile and no observed treatment-related adverse events. SwanBio will present additional data during the AAN virtual meeting April 24-26, 2022.

“The data we’re sharing at AAN this year demonstrate the potential of SBT101 to safely and effectively establish ABCD1 gene expression in the spinal cord, directly addressing the underlying cause of AMN,” said Karen Kozarsky, Ph.D., SwanBio’s chief scientific officer. “These data represent the tremendous progress we’ve made to date on our pipeline and scientific platform. The results reinforce the foundation of our pipeline, including our unique expertise in biodistribution to the spinal cord, which we plan to leverage to pursue other spinal cord-related indications in the future.”

The ABCD1 mutation in people living with AMN disrupts the function of cells in the spinal cord and other tissues, leading to nerve degeneration and often adrenal gland dysfunction, causing the symptoms of the disease. These symptoms include loss of mobility in adulthood, incontinence, and sexual dysfunction, which all negatively impact quality of life. SBT101 is designed to increase ABCD1 expression and address the root cause of the disease.

Summary of Findings

• In NHPs, data now out to six months demonstrated that intrathecal (IT) administration of SBT101 resulted in:
  • Widespread, detectable tissue-specific distribution of vector genomes and expression of ABCD1 mRNA
  • Histopathological findings consistent with those typically observed for AAV9, including mild to moderate changes in axonal degeneration and neuronal necrosis
  • The presence of AAV neutralizing antibodies in serum but no persistent levels in cerebrospinal fluid
  • Good tolerability with no adverse events or clinical observations related to SBT101, consistent with previous findings
• In NHPs, biodistribution of IT-administered AAV9 to investigate infusion parameters and effect on biodistribution throughout the spinal cord and dorsal root ganglia (DRG), demonstrated:
  • Administration of AAV9 over a 24-hour period provided more widespread transduction of the spinal cord and DRG as compared to bolus administration
  • Biodistribution following six-hour administration was equivalent to that at 24 hours, which is a more optimal duration of administration in the clinical setting
• In mouse models of AMN, administration of SBT101 resulted in sustained hABCD1 transgene expression through six months duration, with minor to undetectable white matter pathological findings in the spinal cord, along with demonstrated biologic activity, building upon data presented at the European Society of Gene and Cell Therapy (ESGCT) Annual Meeting in October 2021.

Presentation Details
Scientific Session S29.002: Preclinical Pharmacology and Toxicology of Intrathecally Infused AAV9-hABCD1, a Gene Therapy Candidate for AMN, in Non-Human Primates
Session: Oral Presentation - Preclinical and Observational Studies of Neuromuscular Diseases
Date & Time: April 6, 2022, 1:12 p.m. PT

Poster Session P12.13-008: Optimization of Intrathecal Delivery of an Infused AAV9 Vector for Delivery of a Gene Therapy Candidate for AMN in Non-Human Primates
Session: Poster Presentation - Neuromuscular Disease: Peripheral Neuropathy 4
Date & Time: April 5, 2022, 5:30 - 6:30 p.m. PT

Virtual Poster Session P1.261: An AAV Encoding Human ABCD1 Shows Dose-Responsive Expression and Function Following Spinal Cord Delivery in a Rodent Model of AMN
Session: Virtual Poster Presentation
Date & Time: Available during the virtual meeting beginning April 24, 2022

About SBT101
SBT101 is the first AAV-based gene therapy candidate cleared by the FDA for human studies, designed to compensate for the disease-causing ABCD1 mutation in people living with adrenomyeloneuropathy (AMN). In preclinical studies, treatment with SBT101 demonstrated dose-dependent improvement of AMN disease markers in mouse models and was shown to be well-tolerated in non-human primates at six months post-treatment. The clinical program for SBT101 builds on this positive preclinical data, plus the company’s deep understanding of the underlying pathophysiology of the disease and the patient experience of AMN, including new insights being gathered in an ongoing natural history study.

SwanBio expects to initiate a randomized, controlled Phase 1/2 clinical trial designed to assess the safety and efficacy of SBT101 in patients with AMN in the second half of 2022. In early 2022, the FDA cleared SwanBio’s Investigational New Drug application for SBT101 and granted SBT101 Fast Track and Orphan Drug Designation.

About Adrenomyeloneuropathy
Adrenomyeloneuropathy (AMN) is a progressive and debilitating neurodegenerative disease caused by mutations in the ABCD1 gene that disrupt the function of spinal cord cells and other tissues. AMN is characterized by loss of mobility in adulthood, incontinence, pain, and sexual dysfunction which all affect quality of life. Between 8,000-10,000 men in the United States and European Union are living with AMN. There are no approved therapies for the treatment of the disease; current standard of care is limited to symptom control.

About SwanBio Therapeutics
SwanBio Therapeutics is a gene therapy company that aims to bring life-changing treatments to people with devastating, inherited neurological conditions. SwanBio is advancing a pipeline of gene therapies, designed to be delivered intrathecally, that can address targets within both the central and peripheral nervous systems. This approach has the potential to be applied broadly across three disease classifications – spastic paraplegias, monogenic neuropathies, and polygenic neuropathies. SwanBio’s lead program is being advanced toward clinical development for the treatment of adrenomyeloneuropathy (AMN). SwanBio is supported by long-term, committed investment partners, including its primary investors Syncona, Ltd. (lead investor and majority shareholder) and Mass General Brigham Ventures. For more information, visit SwanBioTx.com.

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